Mandatory tumor tissue specimens and associated analyses for clinical trial participation appear to be a significant barrier to clinical trial enrollment and may delay treatment. Routine tissue banking at diagnosis, use of available diagnostic samples, less invasive tests, faster turnaround time at central laboratories, and allowing for local testing and more resources for timely tissue collection are potential resolutions for addressing these barriers.

These conclusions were drawn by investigators at Princess Margaret Cancer Center, in Toronto, Canada, in a study published in the Journal of Thoracic Oncology (doi:10.1016/j.jtho.2015.09.006).

Clinical trials are increasingly requiring mandatory submission of archival tumor tissue or repeat biopsies for analysis before patients can be enrolled in the trial. Due to the nature of personalized and precision medicines, more clinical trials are evaluating therapies designed to target a specific alteration within the tumor. Patients are therefore enrolled in the trial based on the presence or absence of the specific alteration or biomarker.

The authors reviewed and prospectively tracked patients with metastatic non-small cell lung cancer (NSCLC) being assessed for systemic therapy clinical trials from January 2007 to March 2015. The study objectives were to determine the impact of the mandatory tissue requirement on the number of patients with advanced NSCLC who were able to enroll and receive therapy; determine the time from initial consent to repeat biopsy and, ultimately, study therapy; and determine the reasons why patients were not eligible for enrollment.

The study analyzed a total of 55 clinical trials, with 54 linked to therapy and 1 for biomarker analysis only. Thirty-two trials allowed the use of archival samples, but 6 trials mandated repeat biopsies. Presence and/or confirmation of a specific biomarker were required by 24 trials. Trial participation was offered to 636 patients at 940 unique study encounters, with some patients enrolling in multiple trials.

In the 54 trials linked to therapy, 549 potential study candidates were screened, and 60% went on to receive the study treatment. More patients received the study treatment when enrolled in trials without mandatory tissue requirement vs those with mandatory tissue requirement (83% vs 55%, P<.0001) and the study treatment was started earlier (median 9 days vs 16 days, P=.002).

In trials permitting archival tissue, 59% of participants received the study therapy, whereas only 38% did when a repeat biopsy was required (P=.0007) and time from consent to therapy was shorter (median 14 days vs 54 days, P<.001).

The most common barriers to trial enrollment included absence of a required biomarker (34%), consent withdrawal (20%), deterioration/death (17%), other exclusion criteria (15%), and insufficient biopsy tissue (10%).

"The consequences of mandatory tumor tissue requirements in advanced NSCLC clinical trials with respect to accrual rates, potential time delays, and patient attrition are sobering for investigators and patients,” said Natasha Leighl, MD, MMSc, senior author of the study. “Our study identifies a need to re-evaluate the role of research biopsies in clinical trials and to implement solutions that will improve patient access to investigational treatment by addressing mandatory tumor tissue requirements."